A general anesthesia for surgical procedure can be defined as a reversible condition in which the patient must be unconscious through the use of a hypnotic agent, relieved of pain through the use of a morphinomimetic agent and whose muscles must be relaxed through the use of curares which facilitate surgical procedure.
This general anesthesia is obtained by inhaling a gas or via intravenous injection of anesthetic agents, or a combination thereof.
The use of intravenous anesthetic agents alone is usual practice. The evaluation of the depth of anesthesia or the dose adjustment of the anesthetic agents is performed using clinical or paraclinical criteria.
At the current time, the dose adjustment of anesthetic agents is performed in relation to somatic changes (movements) or the autonomic nervous system (tachycardia, hypertension, sweating, pupil size) which are caused by surgery or which are an indication of drug under-dosing.
However, the clinical signs are not always specific or may be absent. Movements are no longer a reliable criterion when a curare is used.
Cardiovascular changes are not specific to the anesthetic agents used and may be related to surgery (bleeding, vessel clamping . . . ) or to the patient (high blood pressure, cardiovascular treatments . . . ).
Target-controlled intravenous anesthesia also called TCI (target-controlled infusion) is a method used for the titration of the injected hypnotic agent or morphinomimetic agent.
This method consists of using a pharmacokinetic model of the agent which calculates a plasma concentration and/or <<effect site>> concentration i.e. in the cerebral region, on the assumption that there is a relationship between the calculated concentration and the effect of the drug.
However, the concentrations calculated by the models have very poor correlation with the clinical condition of the patient, and the use thereof has not shown any improvement in the management of patients undergoing surgery compared with standard usage (i.e. dose-weight infusion) of the same anesthetic agents.
The advantage of TCI tooling is that of providing doctors with the possibility to adapt dosages quicker than with variations expressed as weight concentrations.
The presence of an anesthesiologist therefore remains essential during anesthesia.
However an anesthesiologist is not always available in emergency situations, in military conflict or when the patient cannot be moved.
One method for measuring the depth of anesthesia or the effect of anesthetic agents is to measure the patient's electro-cortical activity or electroencephalogram (EEG).
Anesthetic agents modify the morphology of the EEG signal in a manner specific to each agent. However, only trained electroencephalography technicians are able to detect these changes. EEG measurement has been especially used during research protocols to quantify the effect of anesthetic agents.
Real-time interpretation of EEG changes in the operating room has been facilitated through the introduction of monitors which allow real-time analysis of this EEG signal. These monitors calculate different parameters from the spectral analysis of the EEG and combine these to provide a signal or index of depth of anesthesia.
The BIS monitor by Aspect Medical System Inc. is used to measure the depth of anesthesia by calculating an index number from bispectral EEG analysis. This number varies from 0 to 100, 0 representing an isoelectric tracing or flat and 100 representing a tracing of a patient who is awake. During anesthesia, the recommendation is to hold this number within an interval of 45 and 60 to obtain satisfactory conditions for performing a surgical procedure. With said monitor it is possible to measure the depth of anesthesia and to dose the hypnotic agent.
It has effectively already been proposed to use this BIS index for closed-loop administering of an intravenous hypnotic agent for maintaining anesthesia (see for example document U.S. Pat. No. 7,220,240), or when inducing and maintaining a general anesthesia.
There exists in the state of the art another monitor such as the Entropy monitor for example by Datex-Ohmeda Inc. This monitor quantifies the disorder i.e. the entropy in the EEG signal, this signal for an anesthetised patient being characterised by ample, synchronized and ordered waves, with little disorder and hence low entropy.
It is then sufficient to maintain this index in the 40-60 range to obtain satisfactory conditions for performing surgery. This monitor provides two data items, the first being called “State Entropy (SE),” which measures the depth of hypnosis and the second being called “Response Entropy (RE),” which measures antinociceptive deficiency. This monitor has already been proposed for automated infusion of a hypnotic agent (see for example document U.S. Pat. No. 6,631,291).